Unveiling autonomic failure in synucleinopathies: Significance in diagnosis and treatment

In movement disorders, motor signs have dominated the attention of clinicians and researchers. However, it is increasingly acknowledged that these diseases also involve non-motor aspects, including autonomic failure, which can be at least as disabling as the movement abnormalities.

Autonomic failure refers to a condition in which one or more components of the autonomic nervous system (ANS) are altered . It is frequently encountered in synucleinopathies such as multiple system atrophy (MSA), Parkinson's disease (PD), Lewy body disease (LBD), and pure autonomic failure (PAF). Severity and precocity vary according to pathology. Cardiovascular autonomic failure is characterized most prominently by neurogenic orthostatic hypotension (OH). OH causes disabling symptoms that have a negative impact on quality of life, and it can influence morbidity and mortality rates due to the risk of falls and the increased incidence of myocardial infarction, stroke, and heart failure [1].

Exploring autonomic failure has diagnostic and prognostic value but requires specific and sometimes invasive techniques. Moreover, certain organs are difficult to explore, and the identification of latent urogenital or digestive autonomic failure often remains the domain of the corresponding specialty. In synucleinopathies, the autonomic items of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [2] and Unified Multiple System Atrophy Rating Scale (UMSARS) [3] can be useful for screening autonomic failure. Specific questionnaires are also available: the Scales for Outcomes in PD-Autonomic (SCOPA-AUT) [4] and the Composite Autonomic Symptom Scale (COMPASS) [5] are the most widely used and the most effective for the detection of OH [6].

In this review, we describe the main clinical tools commonly used to assess ANS status, focusing on cardiovascular autonomic failure, which is more easily studied in neurology. In addition, we will discuss implications for diagnosis and treatment of cardiovascular autonomic failure in synucleinopathies.

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